Among those viruses which cause ocular infections none are more pervasive and devastating than herpes simples virus (HSV). This virus accounts for an estimated 300,000-500,000 cases annually. A number of studies have shown that the T lymphocyte response is a critical factor in resolving HSV infections including ocular disease. However, precisely how th T cell response is regulated, and how it may be manipulated to the host's kadvantage remain a long sought goal. Recently, prospects for obtaining a more detailed understanding of the immune response to virus infection have been greatly enhanced by the development of new techniques which enable one to clone normal immunocompetent cells. The monoclonal cell lines that are generated can be maintained in vitro and expanded as desired. Most importantly, the cells retain their specificity and function. Thus, antigen specific T cell clones are a powerful tool which will be immensely useful for investigating various aspects of lymphocyte interaction not previously possible using coventional cell-culture techniques. The specific goal of this proposal is to employ the new technology to develop cloned T cell lines specifically reactive to HSV type 1 antigens. Draining lymph node cells collected from HSV-1 sensitized mice will be culture in vitro with virus antigen and irradiated syngeneric spleen cells. Cultures will be restimulated every 10-14 days, and tested for responsiveness in T cell proliferation and cytotoxicity assays. Positive lines will be cloned as described by Infante et al (J. Exp. Med., 154, 1342, 1981), and characterized with respect to membrane antigent content using commercially aviilable monoclonal lantibody of appropriate specificity. Antigen reactive cloned lines will be evaluted for thjeir therapeutic efficacy in Balb/c mice infected ocularly with HSV-1.